Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas.
Michal Kabza, Justyna A Karolak, Malgorzata Rydzanicz, Michał W Szcześniak, Dorota M Nowak, Barbara Ginter-Matuszewska, Piotr Polakowski, Rafal Ploski, Jacek P Szaflik, Marzena Gajecka
Author Information
Michal Kabza: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.
Justyna A Karolak: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.
Malgorzata Rydzanicz: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
Michał W Szcześniak: Department of Bioinformatics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University in Poznan, Poznan, Poland.
Dorota M Nowak: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.
Barbara Ginter-Matuszewska: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland. ORCID
Piotr Polakowski: Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
Rafal Ploski: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
Jacek P Szaflik: Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
Marzena Gajecka: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.
To understand better the factors contributing to keratoconus (KTCN), we performed comprehensive transcriptome profiling of human KTCN corneas for the first time using an RNA-Seq approach. Twenty-five KTCN and 25 non-KTCN corneas were enrolled in this study. After RNA extraction, total RNA libraries were prepared and sequenced. The discovery RNA-Seq analysis (in eight KTCN and eight non-KTCN corneas) was conducted first, after which the replication RNA-Seq experiment was performed on a second set of samples (17 KTCN and 17 non-KTCN corneas). Over 82% of the genes and almost 75% of the transcripts detected as differentially expressed in KTCN and non-KTCN corneas were confirmed in the replication study using another set of samples. We used these differentially expressed genes to generate a network of KTCN-deregulated genes. We found an extensive disruption of collagen synthesis and maturation pathways, as well as downregulation of the core elements of the TGF-β, Hippo, and Wnt signaling pathways influencing corneal organization. This first comprehensive transcriptome profiling of human KTCN corneas points further to a complex etiology of KTCN.
